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A Fast and reliable spectroscopic method for the determination of membrane-water partition coefficients of organic compounds

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Lipids

Abstract

Partition coefficients (K p ) between egg yolk phosphatidylcholine multilamellar vesicles and water were determined for two nonsteroidal anti-inflammatory drugs (indomethacin and acemetacin) using two independent methodologies: derivative spectrophotometry and variation of the experimental acidity constant in the presence of increasing vesicle concentration. Second-derivative spectrophotometry allowed for total elimination of background signal effects arising from lipid vesicles, without the need for separation techniques that may disturb equilibrium states. By using a model based on a simple partition, the values of K T p can be obtained directly; furthermore, by performing determinations at two different pH values it is possible to calculate partition coefficients for the neutral and negatively charged forms of the drugs (K AH p and K A p ). In the other methodology, values of apparent acidity constants (K app) were determined by spectrophotometry at different pH values and different lipid concentrations, and an increase in K app with decreasing lipid concentration was observed for both drugs, and from this dependence it was possible to calculate K AH p and K A- p for each drug. These values were used as a check for those obtained by derivative spectroscopy, which has proven to be a reliable and more expeditious method to obtain K AH p and K A- p .

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Abbreviations

EPC:

egg yolk phosphatidylcholine

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Authors and Affiliations

  1. CEQUP/Departamento de Química, Faculdade de Ciências, Universidade do Porto, Porto, Portugal

    Baltazar de Castro & Paula Gameiro

  2. CEQUP/Departamento de Química-Física, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal

    José L. F. C. Lima, Carla Matos & Salette Reis

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  1. Baltazar de Castro
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  2. Paula Gameiro
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  3. José L. F. C. Lima
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  4. Carla Matos
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  5. Salette Reis
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Correspondence to Salette Reis.

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de Castro, B., Gameiro, P., Lima, J.L.F.C. et al. A Fast and reliable spectroscopic method for the determination of membrane-water partition coefficients of organic compounds. Lipids 36, 89–96 (2001). https://doi.org/10.1007/s11745-001-0673-0

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  • DOI: https://doi.org/10.1007/s11745-001-0673-0

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